The product that will be developed by MedVas Concepts is a drug targeting vehicle for cancer therapeutics used in combination with radiation therapy. The product uses a feature of ionizing radiation to match drug delivery selectivity with that of the radiation treatment. More than 50% of cancer patients receive radiation therapy, or chemotherapy, or a combination of both. While modern radiation therapy techniques are highly tunable to tumor locations, combination therapies are limited by the poor selectivity of most systemic chemotherapy strategies. We have recently patented a drug targeting system that selectively delivers chemotherapeutics to tumor endothelial cells using cell surface proteins that are upregulated by exposure to ionizing radiation. We have demonstrated that surface targets are significantly upregulated by exposure to radiation therapy, and that various molecules can be used to ensure that both core and peripheral cancer tissues are targeted. We have demonstrated that our system can be used to control tumor growth in a rodent model, and that multiple targeting ligands increase delivery efficiency. In this Phase 1 proposal, we intend to demonstrate proof-of-concept that a bifunctionalized format of our product can selectively deliver a vascular disrupting agent to endothelial cells, and more effectively and safely inhibit tumor growth in an animal model of disease. PUBLIC HEALTH RELEVANCE: This proposal will increase the effectiveness and safety of combined radiation and chemotherapies for cancer treatment. Current combined treatments are limited by the poor cancer-selectivity of drugs. The product being developed here will be the first drug delivery system that uses focused radiation to guide chemotherapeutic agents to cancer cells, while sparing normal tissues from side effects.